A Reactivity-Based 18F-Labeled Probe for PET Imaging of Oxidative Stress in Chemotherapy-Induced Cardiotoxicity
| Autor: | Pragalath Sadasivam, Filipa Mota, Victoria R. Pell, Richard Southworth, Nisha Singh, Ran Yan, Friedrich Baark, Edward C. T. Waters |
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| Rok vydání: | 2021 |
| Předmět: |
Cardiac function curve
Pharmaceutical Science Pharmacology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Drug Discovery Medicine 030304 developmental biology chemistry.chemical_classification 0303 health sciences Cardiotoxicity Reactive oxygen species medicine.diagnostic_test business.industry Superoxide Cancer medicine.disease 3. Good health chemistry reactive oxygen species oxidative stress cardiotoxicity PET imaging fluorine-18 Positron emission tomography 030220 oncology & carcinogenesis Molecular Medicine business Oxidative stress |
| Zdroj: | Mota, F, Pell, V, Singh, N, Baark, F, Waters, E, Sadasivam, P, Southworth, R & Yan, R 2022, ' A reactivity-based 18F-labeled probe for PET imaging of oxidative stress in chemotherapy-induced cardiotoxicity ', Molecular Pharmaceutics, vol. 19, no. 1, pp. 18-25 . https://doi.org/10.1021/acs.molpharmaceut.1c00496 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.1c00496 |
| Popis: | Oxidative stress underlies the pathology of many human diseases, including the doxorubicin-induced off-target cardiotoxicity in cancer chemotherapies. Since current diagnostic procedures are only capable of monitoring cardiac function, a noninvasive means of detecting biochemical changes in redox status prior to irreversible functional changes is highly desirable for both early diagnosis and prognosis. We designed a novel 18F-labeled molecular probe, 18F-FPBT, for the direct detection of superoxide in vivo using positron emission tomography (PET). 18F-FPBT was radiosynthesized in one step by nucleophilic radiofluorination. In vitro, 18F-FPBT showed rapid and selective oxidation by superoxide (around 60% in 5 min) compared to other physiological ROS. In healthy mice and rats, 18F-FBPT is distributed to all major organs in the first few minutes post injection and is rapidly cleared via both renal and hepatobiliary routes with minimal background retention in the heart. In a rat model of doxorubicin-induced cardiotoxicity, 18F-FBPT showed significantly higher (P < 0.05) uptake in the hearts of treated animals compared to healthy controls. These results warrant further optimization of 18F-FBPT for clinical translation. |
| Databáze: | OpenAIRE |
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